Disulfide reduction, enzyme regulation

Phosphorylation, Adenylylation, and Disulfide Reduction Lead to Reversible Covalent Modifications Allosteric Regulation Allows an Enzyme to Be... 

Some Enzymes Regulated by Disulfide Reduction in Plants... 

D. M. Ziegler, Role of reversible oxidation-reduction of enzyme thiols-disulfides in metabofic regulation, Annu. Rev. Biochem., 54 (1985) 305-329. 

Glucose 6-phosphate dehydrogenase, the first enzyme in the oxidative pentose phosphate pathway, is also regulated by this light-driven reduction mechanism, but in the opposite sense. During the day, when photosynthesis produces plenty of NADPH, this enzyme is not needed for NADPH production. Reduction of a critical disulfide bond by electrons from ferredoxin inactivates the enzyme. 

A reversible covalent modification that plants use extensively is the reduction of cystine disulfide bridges to sulf-hydryls. Many of the enzymes of photosynthetic carbohydrate synthesis are activated in this way (table 9.3). Some of the enzymes of carbohydrate breakdown are inactivated by the same mechanism. The reductant is a small protein called thioredoxin, which undergoes a complementary oxidation of cysteine residues to cystine (fig. 9.5). Thioredoxin itself is reduced by electron-transfer reactions driven by sunlight, which serves as a signal to switch carbohydrate metabolism from carbohydrate breakdown to synthesis. In one of the regulated enzymes, phosphoribulokinase, one of the freed cysteines probably forms part of the catalytic active site. In nicotinamide-adenine dinucleotide phosphate (NADP)-malate dehydrogenase and fructose-1,6-bis-... 

FTR plays the central role in light regulation of the activity of enzymes involved in oxygenic photosynthesis. The light signal is converted into reducing equivalents in the form of reduced 2Fe Fd by photosystem I and FTR catalyzes the reduction of disulfides in thioredoxin (Trx) / and m using the... 

ADP-Glc PPase from potato tuber has an intermolecular disulfide bridge that links the two small subunits by the Cys residue it can be activated by reduction of the Cys disul-hde linkage (46). At low concentrations (lOjxM) of 3-PGA, both spinach leaf reduced thioredoxin/ and m reduce and activate the enzyme. Fifty percent activation was observed for 4.5-and 8.7- xM reduced thioredoxin/ and m (47). The activation was reversed by oxidized thioredoxin. Cys is conserved in the ADP-Glc PPases from plant leaves and other tissues except for the monocot endosperm enzymes. In photosynthetic tissues, this reduction may also be physiologically pertinent in the hne regulation of the ADP-Glc PPase. 

Genetic methods provide a powerful approach to the biosynthetic introduction of redox groups [including cysteine residues as well as unnatural redox active amino acids (79)] into proteins. As an example, a disulfide bridge inserted across the active site of T4 lysozyme has been used to create a redox mechanism for regulating enzyme activity (SO). Oxidation of the cysteines to form the disulfide closes the active site region, whereas reduction exposes the active site and restores catalytic activity. 

ACC regulation in cells is poorly understood, but redox control and phosphorylation are probably key factors. In pea, activation was found to be mediated through reduction of a disulfide bond between the a-CT and the j8-CT subunits [19]. Plastid ACC is likely to be subject to redox regulation similar to that of several key enzymes of photosynthesis. 

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